We will evaluate the effects of deep brain stimulation (DBS) of bilateral nucleus accumbens (NAc) added to background treatment for treatment refractory Methamphetamine Use Disorder (MUD). This is a small randomized cross-over study to demonstrate feasibility and safety, test treatment outcomes (use, craving), and identify novel biological targets (NAc local field potentials (LFP) and functional MRI).
In a randomized cross-over design of DBS of the nucleus accumbens (NAc) for treatment refractory methamphetamine use disorder (MUD, n=5), we will test safety, feasibility, effect on clinical outcomes (craving and use), and seek to identify biological targets (using cue craving during recording of local field potentials and MRI).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
2
6 months of active stimulation -- \> 6 months of sham stimulation
6 months of sham stimulation -- \> 6 months of active stimulation
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
Incidence of study-emergent adverse events
Participants will be closely monitored for adverse events throughout the study including regular meetings with study staff and administration of the COMBINE SAFTEE during each programming session.
Time frame: 56 weeks
Methamphetamine use
Operationalized as the highest number of consecutive days of no methamphetamine use in the final month of sham vs. final month of active stimulation.
Time frame: Measured during weeks 26-30 and weeks 52-56 (last month on stimulation and sham)
Methamphetamine use
Operationalized as the number of days methamphetamine is used in the final month of sham vs. final month of active stimulation.
Time frame: Measured during weeks 26-30 and weeks 52-56 (last month on stimulation and sham)
Methamphetamine craving
Measured weekly using the Stimulant Craving Questionnaire-Brief where each item is scored 0-6 (from Strongly Disagree=0 to Strongly Agree=6) with items #4 and #7 reverse scored. We will average all 10 items as the total score, with higher scores indicating greater levels of craving in the final month of sham vs. final month of active stimulation.
Time frame: Comparing weeks 26-30 and weeks 52-56
Local Field Potential
Electrophysiologic data - three types of LFP data that will be collected: (a.1) BrainSense™ Streaming assessed in the laboratory during the cue-craving task at baseline, 6, and 12 months; (a.2) BrainSense™ Events will be triggered by the participant using the patient programmer when he/she experiences craving; (a.3) BrainSense™Timeline records 10 minute averages of power spectral data within a 5 Hz window throughout the 12 month UG3 trial.
Time frame: baseline through week 56
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MRI
Cue craving MRI data will be collected at baseline, week 30 and week 56
Time frame: 56 weeks
MRI
Resting state MRI data will be collected at baseline, week 30 and week 56
Time frame: 56 weeks
Behavioral Inhibition System/Behavioral Approach System (BIS/BAS)
BIS/BAS will be collected at baseline, week 30 and week 56 Behavioral inhibition system score, assessing tendency to withdraw from aversive conditioned stimuli, and a behavioral activation score assessing tendency to approach appetitive stimuli. This is a 24-item scale with all items rated on a 4 point scale. With appropriate reverse scoring, this will be used to create BIS score (items 2, 8, 13, 16, 19, 22, 24), BAS Drive (items 3, 9, 12, 21), BAS Fun Seeking (5, 10, 15, 20) and BAS Reward Responsiveness (items 4, 7, 14, 18, 23) scores.
Time frame: 56 weeks
Impulsiveness
Barratt Impulsiveness Scale (BIS-11) will be collected at baseline, week 30 and week 56 This 30 item measure questionnaire (using a 1-4 scale for each item) generates a total score, along with Attentional, Motor and Nonplanning second order factors.
Time frame: 56 weeks
Sensation seeking
This 40-item questionnaire, measured at baseline, week 30 and week 56, provides, with appropriate reverse scoring, a total score (items 1-40), and 4 subscales: Disinhibition (1, 12, 13, 25, 29, 30, 32, 35, 36), Boredom Susceptibility (2, 5, 7, 8, 15, 24, 27, 31, 34, 39), Thrill and Adventure Seeking (3, 11, 16, 17, 20, 21, 23, 28, 38, 40) and Experience Seeking (4, 6, 9, 10, 14, 18, 19, 22, 26, 37).
Time frame: 56 weeks
Anhedonia
The Snaith-Hamilton Pleasure Scale, measured at baseline, week 30 and week 56, is a 14 item questionnaire (all rated on a 4 point Likert scale) and covers four domains of hedonic experience (interest/pastimes, social interaction, sensory experience and food/drink). With appropriate reverse scoring, we will use total score.
Time frame: 56 weeks
Delay Discounting
The MCQ, measured at baseline, week 30 and week 56, is a 27 item self administered questionnaire that examines delay discounting and can be hand scored using available tables. We will use the mean of the k at indifference between 2 questions that reflect a change between choosing a delayed vs. immediate reward.
Time frame: 56 weeks
Risk taking
Balloon Analog Risk Task (measured at baseline, week 30 and week 56) We will utilize the average number of pumps on un-popped balloons and mean balloons popped.
Time frame: 56 weeks